# Magrolimab Therapy in Conjunction with Conventional Chemotherapeutics Slows Disease Progression in Pediatric Acute Myeloid Leukemia Patient-Derived Xenograft Models

## TL;DR

Magrolimab, when used alone or with chemotherapy, slows disease progression in certain types of pediatric acute myeloid leukemia in animal models.

## Contribution

Magrolimab combined with chemotherapy improves survival and reduces disease burden in pAML xenograft models with KMT2A rearrangements.

## Key findings

- Magrolimab alone improved survival in AML006 and AML013 models with KMT2A rearrangements.
- Ara-C + Magro therapy significantly improved survival and reduced disease burden in all three models.
- Aza + Magro therapy improved survival and reduced disease burden in AML010 and AML013 models.

## Abstract

Magrolimab, an anti-CD47 monoclonal antibody, is a promising targeted agent for pediatric acute myeloid leukemia (pAML), a patient population with a high need for novel therapeutics to improve current poor clinical outcomes. The aim of our study was to assess the efficacy of Magrolimab in three pAML pre-clinical models in combination with the conventional chemotherapy drugs Azacitidine and Cytarabine. Our work showed that Magrolimab, as a single agent or in combination with Cytarabine, was effective in slowing disease progression in pAML pre-clinical models with specific genetic changes, suggesting potential efficacy in subsets of pAML patients. These results highlight the importance of testing novel agents across diverse subtypes of a heterogeneous disease such as AML.

Background/Objectives: Magrolimab (Magro) is a humanized naked anti-CD47 monoclonal antibody that blocks the SIRPα CD47 interaction, allowing macrophages to target and destroy cancer cells. To evaluate its preclinical efficacy in vivo, Magro was tested as a single agent and in combination with conventional chemotherapy drugs, Cytarabine (Ara-C) or Azacitidine (Aza), in three pediatric AML (pAML) patient-derived xenograft (PDX) models—AML006 (KMT2A::MLLT1), AML010 (+10, WT1), and AML013 (KMT2A::MLLT4). Methods: After PDX model establishment, mice were assigned to treatment groups hulgG4 (VC, vehicle control for Magro), Magro, Ara-C + VC, Aza + VC, Ara-C + Magro, and Aza + Magro, and then followed for survival. Mice that met humane euthanasia endpoints and at the culmination of experimental timelines had tissues harvested to measure disease burden. Results: Magro alone significantly improved survival in AML006 (p < 0.0001) and AML013 (p = 0.003) and decreased bone marrow (BM) disease burden in AML006 (p = 0.009) and AML013 (p = 0.002). Ara-C + Magro therapy led to significantly improved survival in all three models and significantly decreased BM disease burden in AML006 (p < 0.0001) and AML013 (p = 0.048). Aza + Magro therapy led to significantly improved survival in AML013 (p = 0.047) and AML010 (p = 0.017) and significantly lower BM disease burden in AML010 (p = 0.001). Conclusions: Interestingly, the two models that demonstrated improvement in survival with Magro harbored KMT2A rearrangements, suggesting a subset of patients that may be more responsive to the effects of CD47 blockade. As this drug is being evaluated for use in other malignancies, future studies may focus on investigating the importance of biomarker-based patient selection.